Raleigh, S. M. (2005) A genomewide linkage study of 1,933 families affected by premature coronary artery disease: The British Heart Foundation (BHF) Family Heart Study. The American Journal of Human Genetics. 77(6), pp. 1011-1020. 1537-6605.
| Item Type: | Article |
|---|---|
| Abstract: | Coronary artery disease (CAD) and its most important complication, myocardial infarction (MI), are the leading cause of premature death in the Western world. CAD has a substantial genetic basis, especially when it occurs early. We investigated the genetic determinants of premature CAD by performing a genomewide linkage analysis of 4,175 affected subjects from 1,933 families recruited throughout the United Kingdom. Each family had at least two available siblings with CAD, with validated onset before age 66 years. Linkage analysis was performed using 416 microsatellite markers. We observed suggestive linkage, for both CAD and MI, to a region on chromosome 2. For CAD, a LOD score of 1.86 was observed at marker D2S2271, which, in an ordered subset analysis, increased to 2.70 in families (n=1,698) with a minimum age at diagnosis of 56 years or younger. For MI, an overlapping peak with a LOD score of 1.15 was observed at marker D2S2216, which increased to 2.1 in families (n=801) with a minimum age at diagnosis of 59 years or younger. Exclusion mapping showed that 100% of the autosomal genome could be excluded for locus-specific sibling relative risks of 1.5 and 1.6 for CAD and MI, respectively. The region identified on chromosome 2 overlaps linked regions observed in two other smaller genome scans for CAD. Together, these findings strongly suggest that there is a locus on chromosome 2 that influences coronary atherosclerosis risk. The exclusion of a common locus that increases risk of CAD to siblings by >50% has important implications for strategies for further defining the genetic basis of CAD |
| Subjects: |
R Medicine > RC Internal medicine > RC666 Diseases of the circulatory (Cardiovascular) system R Medicine > RB Pathology > RB151 Theories of disease. Etiology. Pathogenesis > RB155 Medical genetics |
| Creators: | Raleigh, Stuart M |
| Corporate Creators: | The BHF Family Heart Study Research Group |
| Faculties, Divisions and Institutes: |
University Faculties, Divisions and Research Centres - OLD > Research Centre > Institute of Health and Wellbeing > Centre for Physical Activity and Chronic Disease University Faculties, Divisions and Research Centres - OLD > Faculty of Health & Society > Sports, Exercise & Life Sciences Faculties > Faculty of Health & Society > Sports, Exercise & Life Sciences Research Centres > Centre for Health Sciences and Services Research Centres > Centre for Physical Activity and Life Sciences |
| Date: | 1 December 2005 |
| Date Type: | Publication |
| Page Range: | pp. 1011-1020 |
| Journal or Publication Title: | The American Journal of Human Genetics |
| Volume: | 77 |
| Number: | 6 |
| Language: | English |
| DOI: | https://doi.org/10.1086/498653 |
| ISSN: | 1537-6605 |
| Status: | Published / Disseminated |
| Refereed: | Yes |
| URI: | http://nectar.northampton.ac.uk/id/eprint/16 |
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